Thesis

SERS-active peptide nanoparticles for investigating protein allostery and bionanoassembly

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Awarding institution
  • University of Strathclyde
Date of award
  • 2012
Thesis identifier
  • T13220
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Abstract
  • The tumour suppressor protein, p53, is either mutated or absent in over 50 % of cancers and is negatively regulated by the mouse double minute two protein, MDM2. This thesis presents a novel nanosensing approach to investigate full-length MDM2 interactions with p53, thus providing an allosteric assay for identifying novel binding ligands. SERS (Surface enhanced Raman scattering) - active nanoparticles, functionalized with a p53 peptide mimic, peptide 12.1, display biologically specific aggregation following addition of MDM2. The extent of nanoparticle assembly is altered following the introduction of various MDM2 binding ligands. This is the first study to report nanoparticle assembly through specific protein-peptide interactions which can be followed by SERS. This approach lends itself to the development of a screening assay for identifying new MDM2 inhibitory molecules and a pilot screen of natural products is completed. Owing to their biocompatibility, peptide functionalized nanoparticles have attracted increasing interest over the last decade for use in numerous biological applications applications. Controlling the assembly of peptide nanoparticles is of particular interest in the development of biocompatible nanomaterials. Coiled coil peptides have demonstrate highly specific binding activity in a variety of cellular functions and their structure is well understood. Work presented in chapter 4 of this thesis documents pH sensitive nanoparticle assembly driven by coiled coil heterodimer formation. SERSactive nanoparticles were functionalized with glutamic acid and lysine rich coiled coil peptides and assembly was observed, monitored using SERS, in heterogeneous solutions. This is the first instance of coiled coil directed assembly of silver nanoparticles followed by SERS.
Resource Type
DOI
Date Created
  • 2012
Former identifier
  • 947841

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